ON THE MEASUREMENT AND INTERPRETATION OF BIRTH-DEFECT ASSOCIATIONS IN EPIDEMIOLOGIC STUDIES
ON THE MEASUREMENT AND INTERPRETATION OF BIRTH-DEFECT ASSOCIATIONS IN EPIDEMIOLOGIC STUDIES
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DOI：
10.1002/ajmg.1320370213
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发表时间：
1990-10-01
期刊：
影响因子：
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通讯作者：
ERICKSON, JD
中科院分区：
文献类型：
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作者：
KHOURY, MJ;JAMES, LM;ERICKSON, JD
同一婴儿中 2 个或更多缺陷的聚集程度可以表示为观察到的具有缺陷的婴儿数量 (O) 与此类婴儿的预期数量 (E) 的比率。预期值通常源自个体缺陷总体率的乘积。由于许多缺陷组合都获得了大的 O/E 比，因此有人认为缺陷的聚类是普遍化的且非特异性的。为了控制缺陷非特异性聚集的趋势，另一种方法是仅在多畸形婴儿中进行相同的计算。该方法的一个主要限制是它针对所有缺陷的聚类趋势进行调整，而不是针对感兴趣的缺陷进行调整，这通常会导致虚假的低 O/E 比。我们提出了一种新方法来调整缺陷之间非特异性聚类的趋势，从而克服了这一限制。通过这种方法，调整后的 O/E 比率与多畸形且具有一项或多项所检查缺陷的婴儿比例成反比。使用来自亚特兰大大都会先天性缺陷计划的数据，我们将此方法应用于先前描述的 VACTERL 缺陷和中线或“分裂”缺陷之间的关联。我们表明，调整后的 O/E 比值大于使用多畸形婴儿获得的值。对于中线缺陷，许多调整后的比率接近于 1，表明这些缺陷的非特异性聚集。最后，以异维A酸胚胎病为例，我们表明 O/E 比率高度依赖于人群中的暴露频率，因此，应谨慎解释它们。
The extent of clustering of 2 or more defects in the same infant can be expressed as the ratio of the observed number of infants with the defects (O) over the expected number of such infants (E). The expected is usually derived from the product of population rates of individual defects. Because large O/E ratios are obtained for many defect combinations, it has been suggested that clustering of defects is generalized and nonspecific. To control for the tendency of nonspecific clustering of defects, an alternative method is to perform the same calculations among multimalformed infants only. A main limitation of this method is that it adjusts for the clustering tendency of all defects rather than the ones of interest, often resulting in spuriously low O/E ratios. We present a new method to adjust for the tendency for nonspecific clustering between defects that overcomes this limitation. With this method, adjusted O/E ratios are inversely related to the proportion of infants who are multimalformed and have one or more of the defects being examined. Using data from the Metropolitan Atlanta Congenital Defects Program, we apply this method to the previously described associations among VACTERL defects and midline or "schisis" defects. We show that adjusted O/E ratios obtained are greater than those obtained by using multi-malformed infants. For midline defects, many of the adjusted ratios were close to one, indicating nonspecific clustering of these defects. Finally, using the example of isotretinoin embryopathy, we show that O/E ratios depend highly on the frequency of exposure in the population, and thus, they should be interpreted with caution.